Letter

TADS study raises concerns

EDITOR—We have additional concerns to those raised byLenzer about the adolescents with depression study (TADS).12

TADS consists of two separate randomised studies: a double blindcomparison of fluoxetine (109 subjects) with placebo (112),and an unblinded comparison between cognitive behaviour therapyalone (111) and fluoxetine plus cognitive behaviour therapy(107). The lack of patient blinding and placebo control in thelatter group is likely to exaggerate the benefit seen in thefluoxetine plus cognitive behaviour therapy group, who receivemore face to face contact and know (as do their doctors) thatthey are not receiving placebo.

Comparing results across all four groups is therefore misleading.The authors' claim that a cognitive behaviour therapy plus placeboarm would have been both too expensive and too artificial tohave clinical relevance is unconvincing.

TADS found no statistical advantage of fluoxetine over placeboon the primary end point, the children's depression rating scale(CDRS-R; P = 0.10), but this was not mentioned in the abstract.This and the small or absent advantages of fluoxetine on otherend points (table) and in other studies,3 shows that fluoxetine,like all other antidepressants, is of doubtful clinical importancefor children.

Adverse events and suicidal behaviour may be greater than theTADS paper says. Despite small numbers, more subjects leavingthe study than reporting adverse effects, and the splittingof adverse events into multiple groups, significantly more psychiatricadverse events occurred in the fluoxetine group than the placebogroup (2 test (1 df), P = 0.047). Despite small numbers andthe exclusion of known suicidal behaviour, TADS found a trendto more suicidal behaviour (six attempts in the fluoxetine groupsand one attempt in the non-fluoxetine groups), consistent withother trials of selective serotonin reuptake inhibitors (SSRIs).We are less reassured than the authors by the fact that no attemptwas fatal. Suicide is a rare event so that a study the sizeof TADS should be expected to miss a significantly increasedrisk.

The data do not support the TADS authors' optimistic conclusions.The balance between benefit and harm of SSRI treatment for depressionin childhood and adolescence has yet to be shown to be favourable.